tbuckley/cabot-search huggingface dataset:
Survival outcome of patients with relapsed or refractory classical Hodgkin lymphoma who achieved remission during immune checkpoint inhibitors treatment.
Authors: Weiping Liu, Ningjing Lin, Yan Xie, Xiaopei Wang, Yuqin Song, Jun Zhu
Journal: Journal of Clinical Oncology (2022)

e19531 Background: Immune checkpoint inhibitors (ICIs) showed strong activity and tolerable toxicity in those patients with relapsed or refractory classical Hodgkin lymphoma. However, there was limited data on the long-term survival outcome of those patients after remission due to ICIs treatment. Methods: The data was collected from 4 pivotal phase 2 clinical trials: AK105-201 (penpulimab, NCT03722147), BGB-A317 (tislelizumab, NCT03209973), SHR-1210 (camrelizumab, NCT03155425), GLS-010 (zimberelimab, NCT03655483). The key inclusion criteria included age ≥18 years, relapsed or refractory classical Hodgkin lymphoma, lines of prior chemotherapy ≥ 2, treated with ICIs monotherapy, achieving complete remission (CR) or partial remission (PR). The progression-free survival (PFS) and overall survival (OS) were estimated from the time of registration. Results: Among 324 screened patients, 260 patients (140 with CR, 120 with PR) were enrolled. The median age was 32 years with a male/female ratio of 1.3:1. The median lines of prior chemotherapy was 3 (range, 2-11). Additionally, 184 patients had refractory disease, and 54 patients received autologous stem cell transplantation (n = 45) or brentuximab vedotin (n = 9). With a median follow-up period of 31.1 months, 116 (44.6%) patients underwent disease progression and 18 (6.9%) patients died. The 3-year PFS and OS rates of 55.1% and 89.7% for all patients, respectively. Compared with those with CR, patients with PR had inferior survival outcome (3-year PFS, 29.5% vs. 72.3%, P &lt; 0.001; 3-year OS, 81.5% vs. 94.4%, P = 0.017). In terms of duration of treatment, the 3-year PFS and OS rates were 28.6% and 71.6%, and 74.5% and 98.5% for patients with duration of treatment &lt; 24 and &gt; 24 month, respectively ( P values were both &lt; 0.001). Among patients with CR, longer duration of treatment (&gt; 24 month) remained positive impact on the survival outcome (3-year PFS, 81.3% vs. 47.1%, P &lt; 0.001; 3-year OS, 98.1% vs. 82.9%, P &lt; 0.001). Conclusions: Deeper remission and longer duration and led to favorable survival outcome for patients with relapsed or refractory classical Hodgkin lymphoma who achieved remission during ICIs treatment.
Energy source comparison in en-bloc resection of bladder tumor: A step to energy indication
Authors: P. Diana, A. Gallioli, A. Territo, A. Piana, M. Fontana, F. Algaba, J. Huguet, Ó. Rodriguez-Faba, J. Aumatell, A. Sanchez-Puy, R. Parada, J. Palou, A. Breda
Journal: European Urology (2022)
Preemptive simultaneous pancreas kidney transplantation has survival benefit to patients
Authors: Enrique Montagud-Marrahi, Elena Cuadrado-Payán, Evelyn Hermida, Judit Cacho, David Cucchiari, Ignacio Revuelta, Jimena del Risco-Zevallos, Nuria Esforzado, Frederic Cofan, Federic Oppenheimer, Vicens Torregrosa, Joana Ferrer, Antoni J. Amor, Enric Esmatjes, Maria José Ramírez-Bajo, Mireia Musquera, Mathew Cooper, Beatriu Bayes, Josep M. Campistol, Fritz Diekmann, Pedro Ventura-Aguiar
Journal: Kidney International (2022)
Tamsulosin as medical expulsive therapy after shock wave lithotripsy for renal stones: A randomised controlled trial (NCT05032287)
Authors: A. Hashem, M. Laymon, M. Elgamal, D.E. Sharaf, A.M. Elmeniar, A.E. Elzalouey, M.M. Abdellutif, R.F. El-Baz, M. Attya, A. Lashin, A.M. El-Assmy, Y. Osman, K. Sheir
Journal: European Urology (2022)
Deep learning-based brain tumor segmentation on limited sequences of magnetic resonance imaging.
Authors: Jacky Huang, Powell Molleti, Michael Iv, Richard Lee, Haruka Itakura
Journal: Journal of Clinical Oncology (2022)

2054 Background: Deep learning algorithms trained to segment brain tumors from magnetic resonance imaging (MRI) perform well in ideal conditions supplied by curated datasets. An example is the MICCAI BraTS 2018 dataset, which provides a set of four MRI sequences (T1, T1 post-gadolinium contrast-enhanced, T2, FLAIR) on 285 samples, along with ground truth segmentations annotated by experts. In real-world settings, however, it is not uncommon for patients to undergo MRI with a limited number of image sequence acquisitions. We examined the effect of restricting the imaging sequence set when training a deep learning model for brain tumor segmentation. Our goal was to identify a limited subset that still achieved acceptably high performance. Methods: In our experiments, we used the convolutional neural network-based U-Net architecture. Instead of the standard BraTS task, we focused on sub-segmenting specific areas of brain tumors: the active, enhancing tumor (AT) and the tumor core (TC; AT plus the cystic/necrotic core). We trained the architecture on 285 samples of the BraTS 2018 dataset using one or both of two sequences: T1 contrast-enhanced (T1CE) and FLAIR. Using each training model, we predicted segmentation masks given a volumetric MR image of a brain tumor on 66 samples in the held-out validation dataset. We submitted the predicted segmentations to the Center for Biomedical Image Computing and Analytics (CBICA) imaging portal for evaluation, which reports prediction accuracy by returning dice scores on each prediction. Results: As shown in the Table, the U-Net model using T1CE alone yielded high performances, with median dice scores of 0.84461 and 0.88267, when segmenting AT and TC, respectively. On the other hand, using FLAIR alone generated lower performances on the same tasks of segmenting the AT (0.25996) and the TC regions (0.51153). Combining T1CE and FLAIR provided no additional performance improvement compared with T1CE used as a standalone sequence. Conclusions: We achieved high performances in two brain tumor sub-segmentation tasks using a limited number of MRI sequences in training a deep-learning algorithm. T1CE alone produced high performances on both TC and AT segmentations. Given the ubiquity of the T1CE sequence, the ability to achieve high performance tumor segmentations in the face of limited image sequence availability is critical when applying our algorithm in real-world clinical or research settings. [Table: see text]
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si7.svg"><mml:mo>⊥</mml:mo></mml:math>-loss: A symmetric loss function for magnetic resonance imaging reconstruction and image registration with deep learning
Authors: Maarten L. Terpstra, Matteo Maspero, Alessandro Sbrizzi, Cornelis A.T. van den Berg
Journal: Medical Image Analysis (2022)

Convolutional neural networks (CNNs) are increasingly adopted in medical imaging, e.g., to reconstruct high-quality images from undersampled magnetic resonance imaging (MRI) acquisitions or estimate subject motion during an examination. MRI is naturally acquired in the complex domain C, obtaining magnitude and phase information in k-space. However, CNNs in complex regression tasks are almost exclusively trained to minimize the L2 loss or maximizing the magnitude structural similarity (SSIM), which are possibly not optimal as they do not take full advantage of the magnitude and phase information present in the complex domain. This work identifies that minimizing the L2 loss in the complex field has an asymmetry in the magnitude/phase loss landscape and is biased, underestimating the reconstructed magnitude. To resolve this, we propose a new loss function for regression in the complex domain called ⊥-loss, which adds a novel phase term to established magnitude loss functions, e.g., L2 or SSIM. We show ⊥-loss is symmetric in the magnitude/phase domain and has favourable properties when applied to regression in the complex domain. Specifically, we evaluate the ⊥+ℓ2-loss and ⊥+SSIM-loss for complex undersampled MR image reconstruction tasks and MR image registration tasks. We show that training a model to minimize the ⊥+ℓ2-loss outperforms models trained to minimize the L2 loss and results in similar performance compared to models trained to maximize the magnitude SSIM while offering high-quality phase reconstruction. Moreover, ⊥-loss is defined in Rn, and we apply the loss function to the R2 domain by learning 2D deformation vector fields for image registration. We show that a model trained to minimize the ⊥+ℓ2-loss outperforms models trained to minimize the end-point error loss.
Prospective evaluation of a side-specific nomogram to predict extraprostatic extension: Implementation leads to reduced positive surgical margin rates
Authors: J.G. Heetman, T.F.W. Soeterik, A.R. Meyer, J.E. Nuininga, R.J. Van Soest, H.H.E. Van Melick, J-P.A. Van Basten, R.C.N. Van Den Bergh
Journal: European Urology (2022)
<i>Slit </i>mutation as an indicator stratified patients benefit from immune checkpoint inhibitors in NSCLC.
Authors: Aihua Bao, Lele Zhao, Dong-sheng Chen, Si Li, Yangyang Yu, Mingzhe Xiao, Chuang Qi
Journal: Journal of Clinical Oncology (2022)

e14572 Background: Immune checkpoint inhibitors (ICIs), targeting the programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1) or cytotoxic T lymphocyte-associated protein 4 (CTLA-4) have demonstrated impressive anti-tumor efficacy in multiple tumors, particularly non-small cell lung cancer (NSCLC). However, only a minority of patients could clinically benefit from the ICIs. Therefore, it is of vital clinical significance to explore underlyingpredictive biomarkers to identify to identify these most potentially ICIs-benefitable patients. Slits (Slit1, 2 and 3) are highly conserved secreted glycoproteins that play important roles in tumorigenesis, including cancer cell proliferation, motility and angiogenesis. However, its role in lung cancer immunotherapy remains unknown. Here we aimed to explore the association between SLIT and ICIs. Methods: 165 NSCLC patients from three public immunotherapy cohorts (Hellmann 2018, Miao 2018, and Rizvi 2015 cohort) were included to analyze the association between SLIT gene mutation and efficacy of ICI therapy. Genomic, survival and mRNA data of NSCLC patients from the Cancer Genome Atlas (TCGA) database was used to explore the potential mechanisms of anti-tumor immunity. Results: NSCLC patients with SLIT mutation were significantly associated with better PFS (HR = 0.27; 95% CI, 0.14-0.52; P &lt; 0.001), objective response rate (ORR, 63.3% vs 25.2%; P &lt; 0.001) and durable clinical benefit (DCB, 86.7% vs 63.0%; P = 0.048) after ICIs therapy, compared with those with wide-type SLIT. SLIT mutation were associated with increased TMB ( P &lt; 0.001). In the multivariable Cox proportional hazards regression model adjusted by smoking status, PD-L1 expression and TMB, the association between SLIT mutation and PFS remained significant (HR = 0.38; 95% CI, 0.19-0.77; P = 0.007). In contrast, no association between SLIT mutation and OS (LUAD: P = 0.57 ; LUSC: P= 0.1) or PFS (LUAD: P = 0.71; LUSC: P = 0.55) was observed in TCGA datasets, suggesting that SLIT mutation may be a predictive but not a prognostic factor in ICI treatment for NSCLC patients. Based on CIBERSORT-inferred tumor infiltrating lymphocytes from TCGA, SLIT mutation was significantly associated with higher naive B cell, plasma B cell, activated memory CD4+ T cell, CD8+ T cell, as well as lower M2 macrophage and Treg cell. Moreover, SLIT mutation was associated with increased TMB ( P &lt; 0.001) and neoantigen load ( P &lt; 0.001) in TCGA. In addition, GSEA analysis revealed that SLIT mutation was correlated with upregulated DNA damage repair (DDR) signaling pathway and activation of NF-κB in B-cell. Conclusions: Our results demonstrated that SLIT mutation is an underlying classifier that could stratify patients with NSCLC for ICIs. The role of SLIT in immunotherapy is needed to be further studied.
Reply
Authors: Monika Sarkar, Roxanna A. Irani
Journal: Hepatology (2022)

We appreciate the recent response by Ahmad et al. to our manuscript entitled, “Outcomes of pregnancy in autoimmune hepatitis: A population‐based study.” Recall bias was raised as a potential issue, although should be of minimal concern as diagnoses reflect those conditions present during the hospital admission, thus there is a short time period for recall to pose an issue. Miscarriages (defined as pregnancy loss as <20 weeks of gestation) were intentionally excluded to uniformly capture pregnancy events that occur in an inpatient setting at the delivery admission. Contemporary obstetric care offers safe ambulatory management of early miscarriage, and procedures for second trimester losses are often performed at ambulatory surgical centers, neither of which have specific data captured in the high‐fidelity database used in this manuscript. How autoimmune hepatitis (AIH) may influence early pregnancy loss is an important area of future work. As noted in the limitations, International Classification of Diseases coding does not capture AIH disease control or medication regimens. Certainly, an individual’s medication use, how or if the condition leads to early pregnancy loss, and the contribution of other comorbidities (such as antiphospholipid syndrome) is worthwhile and exciting for future research endeavors. We agree that obstetric outcomes for patients with AIH can certainly be favorable, though they warrant close surveillance from an experienced interdisciplinary team. CONFLICT OF INTEREST Nothing to report.
Outcomes following preoperative chemoradiation +/- pazopanib in non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): A report from Children's Oncology Group (COG) and NRG Oncology.
Authors: Aaron R. Weiss, Yen-Lin Chen, Thomas Scharschmidt, Wei Xue, Zhengya Gao, Jennifer O. Black, Julie Fanburg-Smith, Eduardo Zambrano, Edwin Choy, Jessica L. Davis, Mark Kayton, Lynn Million, Scott H. Okuno, Andrew Ostrenga, R. Lor Randall, Stephanie Terezakis, Rajkumar Venkatramani, Dian Wang, Douglas S. Hawkins, Sheri L. Spunt
Journal: Journal of Clinical Oncology (2022)

11504 Background: Pazopanib is a multi-targeted tyrosine kinase inhibitor (TKI) with activity in advanced soft tissue sarcoma. ARST1321 was a phase II study designed to compare the near complete pathologic response rate (≥ 90% necrosis) following preoperative chemoradiation +/- pazopanib in children and adults with intermediate/high risk chemotherapy-sensitive body wall/extremity NRSTS. Enrollment was stopped early following a predetermined interim analysis that found the rate of near complete pathologic response to be significantly greater with the addition of pazopanib. As a planned secondary analysis of the study, we now report the outcome data for this cohort. Methods: ARST1321 was a jointly designed COG and NRG Oncology study open to enrollment July 2014-October 2018. Eligible adult (≥18 years) and pediatric (&lt; 18 years) patients with newly-diagnosed unresected body wall/extremity NRSTS were enrolled into the Chemotherapy Cohort (&gt; 5 cm, FNCLCC grade 2/3, protocol-designated chemotherapy-sensitive histology). Following a dose-finding phase, patients were randomized to receive (Regimen A) or not receive (Regimen B) pazopanib (&lt; 18 years: 350 mg/m 2 /day; ≥ 18 years: 600 mg/day) in combination with ifosfamide (7.5 gm/m 2 /cycle) and doxorubicin (75 mg/m 2 /cycle) + 45 Gy preoperative RT followed by primary resection at week 13, then further chemotherapy to week 25. Results: Eighty-five eligible patients were enrolled in the Chemotherapy Cohort and randomized to receive or not receive pazopanib. Median age 22.1 years (range: 5.7-64.2 years); 30 patients &lt; 18 years. Most common histologies were synovial sarcoma (n = 42) and undifferentiated pleomorphic sarcoma (n = 19). As of December 31, 2021, at a median survivor follow-up of 3.3 years (range: 0.1 – 5.8 years), the 3-year event-free survival (EFS) for all patients in the intent-to-treat analysis was 52.5% (95% CI: 34.8%-70.2%) for Regimen A and 50.6% (32%-69.2%) for Regimen B (p = 0.8677); 3-year overall survival (OS) was 75.7% (59.7%-91.7%) for Regimen A and 65.4% (48.1%-82.7%) for Regimen B (p = 0.1919). Conclusions: Although the rate of near complete pathologic response was significantly greater with the addition of pazopanib to preoperative chemoradiation in children and adults with intermediate/high risk body wall/extremity NRSTS, outcomes were not statistically significantly different between the two regimens. Pathologic response could be a TKI-related phenomenon and may not be a good surrogate marker of outcome in future studies. Clinical trial information: NCT02180867.
DIPG-19. FOXR2 is an oncogenic driver across pediatric and adult cancers
Authors: Jessica W Tsai, Paloma Cejas, Dayle K Wang, Smruti Patel, David W Wu, Phonepasong Arounleut, Xin Wei, Ningxuan Zhou, Sudeepa Syamala, Frank P B Dubois, Alexander Crane, Kristine Pelton, Jayne Vogelzang, Cecilia Sousa, Audrey Baguette, Xiaolong Chen, Alexandra L Condurat, Sarah E Dixon-Clarke, Kevin N Zhou, Sophie D Lu, Elizabeth M Gonzalez, Madison S Chacon, Jeromy J Digiacomo, Rushil Kumbhani, Dana Novikov, J'Ya Hunter, Maria Tsoli, David S Ziegler, Uta Dirksen, Natalie Jager, Gnana Prakash Balasubramanian, Christof M Kramm, Michaela Nathrath, Stefan Bielack, Suzanne J Baker, Jinghui Zhang, James M McFarland, Gad Getz, Francois Aguet, Nada Jabado, Olaf Witt, Stefan M Pfister, Keith L Ligon, Claudia L Kleinman, Henry Long, David T W Jones, Pratiti Bandopadhayay, Timothy N Phoenix
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Understanding how aberrant transcription factors (TFs) hijack normal development to induce oncogenesis is a critical question in oncology. Forkhead box (FOX) proteins are a superfamily of transcriptional regulators characterized by a forkhead DNA-binding domain. Within this family, Forkhead Box R2 (FOXR2) has been identified as a candidate structural variant (SV) driver in a subset of pediatric cancers including CNS embryonal tumors and peripheral neuroblastoma. While FOXR2 has been shown to stabilize MYC isoforms, the mechanistic details through which it enhances tumor formation, other non-SV mechanisms of activating aberrant expression, and the true extent of its role as an oncogene across all cancers have not been systematically evaluated. METHODS: We applied an integrative approach using transcriptomics, epigenetics, in vitro cancer models, and in vivo mouse models to systematically evaluate the mechanisms by which FOXR2 is activated across human cancers. RESULTS: We performed a pan-cancer analysis of FOXR2 activation across over 10,000 adult and pediatric cancer samples, and surprisingly found FOXR2 to be aberrantly upregulated in 70% of all cancer types (including diffuse midline gliomas), and 8% of all individual tumors. FOXR2 expression occurred predominantly in the absence of rearrangement/fusions, single nucleotide variants, or copy number aberrations at the DNA level. Transcriptomic and epigenomic analyses show the vast majority of tumors (78%) aberrantly express FOXR2 through a previously undescribed epigenetic mechanism via hypomethylation of a novel promoter. Using both in vitro and in vivo models, we demonstrate that FOXR2 expression is both sufficient and necessary for transformation across multiple lineages, including DMGs. CONCLUSION: Taken together, this study demonstrates that FOXR2 is a novel and potent oncogene across pediatric and adult cancers, and highlights a new epigenetic mechanism by which its expression is activated.
Cascade Reaction of “Mn<sup>2+</sup>‐Catechol” Triggered by H<sub>2</sub>O<sub>2</sub> to Integrate Firm Tumor Vessel Embolization and Hypoxic Response Relief
Authors: Man Fan, Yiming Liu, Yanqiao Ren, Lu Gan, Yajiang Yang, Hong Wang, Yonggui Liao, Xiangliang Yang, Chuansheng Zheng, Qin Wang
Journal: Advanced Healthcare Materials (2022)

Abstract Transcatheter arterial embolization (TAE) therapy requires firm and long‐term vessel embolization without recanalization. However, firm embolization usually leads to unanticipated hypoxic response which promotes tumor recurrence and metastasis. Herein, an injectable thermosensitive hydrogel containing catechol groups and Mn 2+ (PNDM) has been developed to enhance embolization and inhibit hypoxic response utilizing augmented H 2 O 2 after TAE. This novel embolic agent converts H 2 O 2 into hydroxyl radicals via Mn 2+ ‐dependent Fenton‐like reaction, which are subsequently scavenged through a “catechol‐quinone” transition to suppress hypoxic responses. Quinone structure can not only make hydrogel internal structure more compact, but also enhance hydrogel adhesion to vessel wall. In vivo experiments confirm that the rabbit renal artery can be firmly embolized for 84 days. Studies in liver VX2 tumor‐bearing rabbits demonstrate that the PNDM‐based TAE can promote tumor necrosis, inhibit angiogenesis and tumor metastasis, and greatly prolong rabbit survival. This strategy opens new sights in the TAE therapy for liver cancer.
Outcomes of anti-PD-L1 blockades plus etoposide and platinum (EP) as first-line therapy for extensive-stage small-cell lung cancer (ES-SCLC) with brain metastasis (BM).
Authors: Yaru Tian, Ji Ma, Hui Zhu, Jinming Yu
Journal: Journal of Clinical Oncology (2022)

e20607 Background: Anti-PD-L1 blockades plus EP is the standard first-line therapy for ES-SCLC from IMpower133 and CASPIAN. Subgroup analyses of the two trials indicated that patients (pts) without BMs could benefit from atezolizumab and durvalumab, while those with BMs could not. The aim of the retrospective study is to further investigate the clinical efficacy of the first-line anti-PD-L1 blockades plus EP for ES-SCLC with BMs. Methods: Between 2017 and 2021, pts with newly diagnosed ES-SCLC and baseline BM confirmed by CT or MRI at Shandong Cancer Hospital and Institute were enrolled. According to whether combined with anti-PD-L1 blockades (atezolizumab or durvalumab) or not, pts were assigned to anti-PD-L1+EP group and EP group, respectively. Response was assessed by RECIST 1.1 and survival analyses were conducted using Kaplan-Meier and log-rank tests. Results: A total of 56 pts were enrolled in the current study. Eighteen pts were allocated to anti-PD-L1+EP group and 38 were allocated to EP group. The median follow-up time was 18.17 months. Overall response rate (ORR) was 72.22% vs 78.95% ( P= 0.83) and disease control rate (DCR) was 100% vs 97.37% in the two groups, respectively. And for BMs, the intracranial ORR and DCR were 50.00% vs 68.42% ( P= 0.18) and 72.22% vs 78.95% ( P= 0.83), respectively. Progression-free survival (PFS) was numerically prolonged with anti-PD-L1 blockades, but the significance was not achieved (median: 9.4m vs 7.3m, P = 0.146, HR = 0.63 (95%CI, 0.35-1.13)). The intracranial PFS was not improved, neither (median: 8.2m vs 7.9m, P= 0. 943, HR = 1.02 (0.53-2.00)). However, overall survival was significantly prolonged with anti-PD-L1 blockades (median: NR vs 15.53m, P = 0.012, HR = 0.20 (0.09-0.46)). Conclusions: Collectively, we found that the addition of the first-line anti-PD-L1 blockades to EP brought about a significant survival benefit compared with EP alone for ES-SCLC with BMs.